PubMed Health⌕ Search

Biomedical subjects

D D Despommier

Publications and source records attributed to D D Despommier.

At least 19 recordsLinked to original sources
PubMed1998

How does Trichinella spiralis make itself at home?

The nurse cell-parasite complex of Trichinella spiralis is unlike anything else in Nature. It is derived from a normal portion of striated skeletal muscle cell and develops in a matter of 15 to 20 days after the larva invades that cell type. What are the molecular mechanisms at work that result in this unique relationship? Here, Dickson Despommier presents a hypothesis to account for its formation, in which secreted tyvelosylated proteins of the larva play a central role. These proteins are always present in the intracellular niche of the larva from Day 7 after infection and may be responsible for redirecting host genomic expression, leading to nurse cell formation.

Journal Article↗
PubMed1998

Trichinella spiralis: vascular endothelial growth factor is up-regulated within the nurse cell during the early phase of its formation.

The L1 larval stage of Trichinella spiralis induces modification in a portion of striated skeletal muscle cell resulting in the formation of the nurse cell. This specialized host cell is completely encased in a capsule composed mainly of collagen type IV and type VI, which, in turn, is surrounded by a unique rete of vessels whose formation begins on around day 12 after intracellular infection. We investigated the possibility that vascular endothelial growth factor (VEGF) may be up-regulated during nurse cell formation by employing immunohistochemistry and in situ hybridization on synchronously infected mouse muscle tissue. Both VEGF mRNA and VEGF peptide were detected in the developing nurse cell cytoplasm from day 7 up to 16 mo after infection. In addition, VEGF was also detected in cells in the area immediately surrounding the nurse cell on days 15 and 17. On the basis of these results, we propose that hypoxia is induced by T. spiralis within the developing nurse cell some time prior to the up-regulation of VEGF, perhaps as early as day 7. We further propose, on the basis of the continued presence of VEGF in nurse cell cytoplasm, that a constant state of hypoxia cell is maintained.

Animals↗
PubMed1997

Trichinella spiralis: synthesis of type IV and type VI collagen during nurse cell formation.

The portion of skeletal muscle fiber (Nurse cell) harboring Trichinella spiralis is surrounded by an acellular capsule susceptible to digestion with collagenase. Antibodies recognized type IV and type VI collagen in the capsule, while the periodic acid Schiff reagent stained the capsule differentially, revealing at least two distinct layers. RNA analysis showed that mRNA specific for type IV and type VI collagen was present in muscle tissue on Days 9 and 15, but not on Day 3, following intracellular infection. In situ hybridization showed that most of the mRNA for both types was within the Nurse cell, and all enlarged Nurse cell nuclei were transcriptionally active for those messages. Synthesis of type IV collagen mRNA was absent by Day 24. In contrast, type VI collagen mRNA was still present at 24 days and 8 months. These results support the hypothesis that T. spiralis, either directly or indirectly, influences the synthesis of these two collagen types throughout its own developmental cycle in the Nurse cell.

Animals↗
PubMed1996

Developmental expression of a 43-kDa secreted glycoprotein from Trichinella spiralis.

Trichinella spiralis is an intracellular parasitic nematode that infects skeletal muscle cells. Infection results in loss of tissue specific characteristics and conversion of the muscle cell to a Nurse cell. The characteristic changes leading to the formation of the Nurse cell appear complete by day 12 after intramuscular infection. Proteins synthesized in the stichocytes (secretory cells) of T. spiralis and secreted in the host cell are believed to be involved in the process of Nurse cell formation. One secreted glycoprotein of 43 kDa has been considered as a candidate factor involved in Nurse cell formation. We determined the timing of synthesis and secretion of the 43-kDa glycoprotein and its temporal correlation to the changes of the infected host cell, to gain an understanding of the role of the 43-kDa glycoprotein in T. spiralis infection. We show that the 43-kDa glycoprotein is first expressed on day 11 following intramuscular infection, several days after the changes in the infected muscle cell have been initiated. Protein(s) immunologically related to the 43-kDa glycoprotein but not the 43-kDa glycoprotein itself are detected in the nuclei of mature Nurse cells. During the intramuscular stage the 43-kDa glycoprotein appears to be stored in the alpha-stichocytes of T. spiralis and appears to be secreted immediately following invasion of the intestinal columnar epithelial cells by the L1 larva. The role of the 43-kDa glycoprotein remains unknown, however, these findings argue against involvement of the 43-kDa glycoprotein in Nurse cell formation.

Animals↗
PubMed1996

Trichinella pseudospiralis secretes a protein related to the Trichinella spiralis 43-kDa glycoprotein.

A 43-kDa secreted glycoprotein from the intracellular parasitic nematode Trichinella spiralis has been considered as a factor involved in the formation of the Nurse cell in infected muscle. The closely related intracellular parasitic nematode Trichinella pseudospiralis that also infects muscle cells, does not form Nurse cells and was thought not to secrete the 43-kDa glycoprotein. This implied a unique role for the 43-kDa glycoprotein in T. spiralis infection and supported the hypothesis of involvement of the 43-kDa glycoprotein in Nurse cell formation. Following cloning of a full length cDNA encoding the 43-kDa protein, antibodies were raised against several domains of the 43-kDa glycoprotein. Here we show that a protein related to the 43-kDa glycoprotein exists in T. pseudospiralis. Immunohistochemical studies reveal important similarities in the distribution of the 43-kDa glycoprotein and the related protein from T. pseudospiralis in muscle infections with either of the two parasites. The 43-kDa glycoprotein may therefore play a common role in the life cycles of these two parasites and probably is not involved in Nurse cell formation.

Animals↗
PubMed1996

Clinical aspects of infection with Trichinella spp.

Isolated cases and outbreaks of infection with Trichinella spp. occur frequently throughout the world, sometimes resulting in fatalities. The clinical presentations of signs and symptoms are remarkably constant for most of the species of Trichinella, but in infections with Trichinella nativa and Trichinella britovi, classical symptoms of trichinellosis may be absent. It is important to be able to correlate the clinical presentation of trichinellosis with the life cycle of these helminths in order to make an accurate diagnosis. Knowledge of the epidemiology of the disease enables the physician to identify other potential cases, since most epidemics can be traced back to a common source of raw or undercooked meat. A comprehensive summary relating the most important clinical variables is presented graphically for easy reference to the text. Symptoms and signs are considered in relation to severity of infection. Laboratory findings and diagnostic techniques, including new modalities (e.g., DNA and antigen detection), are discussed. A discussion of treatment and preventive measures concludes our review.

Animals↗
PubMed1995

A method for isolation and partial purification of Trichinella spiralis nurse cells.

Invasion of vertebrate muscle cells by larvae of Trichinella spiralis is accompanied by redifferentiation of the host myofiber into a novel structure called the nurse cell. The nurse cell protects and nurtures the enclosed parasite during its long stay in host muscle. It is anatomically independent of the surrounding uninfected muscle cells and can be isolated from host tissue by mechanical or enzymatic means. Current methods employed for this purpose have yielded only small numbers of nurse cells. An apparatus designed to isolate large numbers of nurse cells and a method for removal of all free larvae and most host muscle debris is described. Homogenization and trypsin digestion of muscle tissue was followed by passage of muscle/parasite suspensions maintained at 37 C through a jacketed glass column fitted with a 40-mesh stainless steel screen at the top and a Nitex screen with 150-microns-diameter pores at the bottom. Nurse cells were retained by the Nitex screen. Density gradient centrifugation using Percoll removed all free larvae and most contaminating muscle debris from nurse cell suspensions. The large quantities of nurse cells made available by this method will allow evaluation of the molecular biology, nutrition, biochemistry, and metabolism of the enclosed parasite and of the Trichinella-modified host muscle cell.

Animals↗
PubMed1993

Trichinella spiralis and the concept of niche.

Trichinella spiralis is an intracellular parasite as both a larva and an adult. The first-stage larva lives in a modified portion of a skeletal muscle cell, the nurse cell, and can reside there for the life span of the host. Adult worms occupy a nonmembrane-bound portion of columnar epithelium, living there as intramulticellular parasites. The newborn larva is the only nonintracellular stage, living free in the circulation. Trichinella spiralis induces modifications in each of its intracellular niches. Parasite signals secreted into the milieu of the developing nurse cell results in the reprogramming of host genomic expression, reflected in loss of muscle-specific proteins, over-expression of collagen, and the development of a circulatory rete. Formation of the nurse cell is complex, presumably involving many steps; yet there is not a large series of related intermediate forms in nature. Trichinella pseudospiralis induces an incomplete nurse cell. Adult parasites cause the death of the infected epithelium. The precise nature of most of the signals from parasite to host and from host to parasite has not been determined. As a direct consequence of exposure to some of them, the host develops long-lasting immunity to reinfection. This may confer advantages both for the parasite, as well as the host, because strong immune responses should reduce intraspecific competition.

Animals↗
PubMed1991

Blood vessels in Trichinella spiralis infections: a study using vascular casts.

Larvae of Trichinella spiralis initiate the transformation of myocytes into nurse cells that become surrounded by elaborate networks of blood vessels. To examine the structure of these networks (i.e., retes), transcardic perfusion was used to clear the vascular tree of Trichinella-infected mice and to inject a plastic that polymerized in situ. Vascular complexes were found only around infected myocytes and were characterized by large circumferential vessels that give rise to the smaller channels of the retes. The secondary vessels vary widely in caliber and are distributed in a random fashion. Three types of network were found: simple, complex, and hypercomplex, and they were distributed normally, with the complex retes the most common. Comparison of the structure of the baskets with that of vessels in surrounding uninfected muscle strongly suggests that the vascular retes are the result of de novo angiogenesis induced during the infection. The parasite may elicit angiogenesis directly through secretion of unique products or may elicit a change in the nurse cell that, in turn, results in growth of new blood vessels.

Animals↗
PubMed1990

Trichinella spiralis: secreted antigen of the infective L1 larva localizes to the cytoplasm and nucleoplasm of infected host cells.

Antibodies were elicited against a purified antigen with an apparent molecular weight of 43K. This antibody preparation also detected a second antigen consisting of a group of closely related components of 45-50K. These antigens are stage specific for the infective first stage larva of Trichinella spiralis and are among the repertoire of secreted antigens originating from the stichosome. Antibody raised against the 43K antigen reacted with the stichosome and cuticle of the mature larva and the cytoplasm and nucleoplasm, but not nucleolus, of all nuclei of infected host cells (Nurse cells) in sections of infected tissues. Studies on sections of synchronously infected muscle tissue revealed that antigen was present only within the worm on Day 7 of the infection. On Day 9 after infection, the stichosome and cuticular surface of the larva and the cytoplasm and nucleoplasm of each nucleus of the Nurse cell reacted with antibody. Nurse cell cytoplasmic and nuclear reactivity increased in intensity until Day 18 after infection. These results suggest that stichocyte-specific antigens are synthesized during the early phase of infection in the muscle, and that as the Nurse-parasite complex develops, some of the antigen is secreted into the milieu of the Nurse cell. The presence of antigen in the cytoplasm and nucleoplasm of the infected host cell is discussed in relation to Nurse cell formation and maintenance.

Animals↗
PubMed1990

Partial characterization of two antigens secreted by L1 larvae of Trichinella spiralis.

Two protein antigens were isolated from excretory-secretory products of Trichinella spiralis by biochemical methods and characterized with respect to their chemical and immunological properties. One antigen, of apparent Mr 43,000, is an abundant secreted protein of infective L1 larvae, while the other, of 45-50 kDa, is present in smaller amounts. Yields, extinction coefficients, isoelectric points, amino acid compositions, and partial N-terminal amino acid sequences for each are reported. Partial amino acid sequences of peptides derived from the 43-kDa protein by cyanogen bromide cleavage have been determined. Treating a reduced-pyridylethylated derivative of the 43-kDa protein with glycopeptidase F (N-glycanase) resulted in formation of a transient product of 37 kDa followed by a stable polypeptide of 32 kDa (by SDS-PAGE), suggesting the presence of two N-linked carbohydrate groups. A similar result was obtained with the 45-50-kDa protein, which gave a transient doublet of 38 and 40 kDa and a final, stable product of 33 kDa, with a minor component of 35 kDa. Two glycosylation sites of the 43-kDa protein and one site of the 45-50-kDa protein can be identified in the amino acid sequences. Polyclonal antibodies prepared against the two proteins cross-reacted extensively, but failed to react with the doubly deglycosylated polypeptides in Western blots. The dominant epitopes present in the reduced-pyridylethylated polypeptides are, therefore, N-linked carbohydrate, although the presence of peptide epitopes in the native proteins cannot be excluded.

Amidohydrolases↗
PubMed1990

Trichinella spiralis: the worm that would be virus.

Trichinella spiralis is one of the world's largest intracellular parasites. Unlike most such organisms, it does not kill the host cell, but induces modifications in cell structure that enhance its own survival. In this article, Dickson Despommier describes the ways in which the parasite uses the cell for its own benefit, and discusses the extent to which this behaviour has contributed to the parasite's success.

Journal Article↗
PubMed1987

Trichinella spiralis: behavior, structure, and biochemistry of larvae following exposure to components of the host enteric environment.

Four layers are present on the surface of infective larvae of Trichinella spiralis isolated from host muscle in pepsin-HCl. Trypsin treatment of pepsin-HCl isolated worms caused partial degradation and removal of large patches of the two outer surface layers. Following exposure to bile, only traces of the outer layers remained on the worms surface. These changes in the worm surface were accompanied by a shift from Type I behavior, typical of pepsin-HCl isolated larvae, to Type II behavior, (snakelike) following exposure to either trypsin or bile. Worm behavior was also temperature dependent. Type I behavior was typical of worms maintained at room temperature regardless of treatment, while Type II behavior displayed by worms held at 37 C was treatment dependent. The absorption of in vitro glucose or beta-methyl-D-glucoside was lowest in pepsin-HCl isolated first stage infective larvae, significantly higher in trypsin treated worms and greatest in worms following exposure to bile. Sugar uptake by worms isolated from the host small intestine after 1 hr of enteral infection was similar to that seen in worms isolated from host muscle in pepsin-HCl. Sugar uptake in vitro in worms 2 hr following enteral infection was similar to worms following exposure to bile. The highest levels of sugar absorption in vitro occurred in worms which had resided in the small intestine for 3 hr. The lowest rates of incorporation of label into worm tissues was seen in 1 hr enteral and pepsin-HCl isolated worms. Infective larvae treated with trypsin or bile incorporated significantly greater amounts of label than the two former groups. The highest levels of incorporation of label into worm tissues was seen in 3 hr enteral worms. These findings support the view that trypsin, bile, and temperature serve as environmental cues which lead to alteration of the parasite's behavioral and nutritional status.

Absorption↗
PubMed1986

Cyclic eosinophilic myositis and hyperimmunoglobulin-E.

A 40-year-old man had regular cyclic episodes of weight gain and eosinophilic myositis associated with hyperimmunoglobulin-E and hypereosinophilia for 9 years. During the episodes his body weight increased up to 10.8%; eosinophil counts reached 41.3 X 10(-9) cells/L; and IgE levels reached 18 000 IU/mL. These values changed regularly in a definite sequence relative to the clinical state. Attempts to document a parasitic cause were unsuccessful, and several courses of anthelmintic therapy were ineffective. An oral dose of prednisone, 10 mg/d, begun in July 1982 resulted in an immediate lessening of the severity of the episodes and a progressive lengthening of the cycle from 35 to 170 days. No further episodes have occurred since March 1984. The patient is fit and well on prednisone therapy, 12.5 mg on alternate days. This apparently unique syndrome has a benign course and is a cyclic disease involving skeletal muscle as the target organ.

Adult↗
PubMed1986

Immunocytolocalization of two protection-inducing antigens of Trichinella spiralis during its enteral phase in immune and non-immune mice.

Monoclonal antibodies (mAb) recognizing epitopes on the 48K (beta stichocyte specific) and the 50/55K antigen (alpha stichocyte specific) were used as first ligands for immunocytolocalization on de-paraffinized sections of infected gut tissue of non-immune and immune CFW strain mice. The enteral phase was studied at 6, 14, 23, 30 hr and 7 days after initiation of infection via the oral route, times corresponding in worm development to the first (L1), second (L2), and third (L3) stage larva and adult. No change in the intensity of the immune reaction with either mAb was noted in parasites developing within immune or non-immune mice for any of the time-points studied. The 48K and the 50/55K antigens were present within the stichocytes at 6 hr. Enterocytes adjacent to some worms also stained positive for both epitopes at this time. Throughout worm development, the amount of each antigen within the worm diminished, until almost none was left at 30 hr. At day 7, the 48K antigen was present within a few stichocyte cells, the canalicular tree, and within the lumen of the midgut. The 50/55K antigen at this time point was localized within only a few stichocyte granules and on the lining of the worm's gut. Embryo stages did not possess either the 48K or 50/55K epitopes. A marked increase in cells bearing IgG in the lamina propria was noted in immune mice when compared with their non-immune counterparts.

Animals↗
PubMed1985

Effects on Trichinella spiralis of host responses to purified antigens.

Purification of two antigens (48-kilodalton polypeptide and a group with major subunits of 50 and 55 kilodaltons) from the infective larvae of the parasitic nematode Trichinella spiralis was recently reported. Immunization of mice with either of these antigens induces strong resistance to a subsequent challenge infection. In the study reported here the mechanism of this resistance was investigated by monitoring the parasite's life cycle in mice immunized with the antigens. Immunized mice were able to expel intestinal adult worms and to inhibit the fecundity of adult female worms at an accelerated rate compared to control mice. Accelerated expulsion and inhibition of fecundity may account entirely for the level of resistance induced by immunization. Although the effects of the immune response apparently are exerted on adult worms, the target antigens are expressed only by developing larvae. This suggests that immune effector mechanisms act on intestinal larvae in such a way that they develop into defective adults.

Animals↗